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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari jennifer c.munoz pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon c.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny cheung jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Phenomenological Based Soft Sensor for Online Estimation of Slurry Rheological Properties

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International Journal of Automation and computing 2019年第5期16卷 696-706页

作者： Jenny L.Diaz c. Diego A.munoz Hernan Alvarez Research Group of Dynamic Processes Universidad Nacional de Colombia-Sede MedellínFacultad de Minas.Cra 80Medellín 65-223Colombia Mathematical Optimization of Processes Centro de Ciencia BásicaUniversidad Pontificia BolivarianaCircular 1Medellín 70-01Colombia

This work proposes a soft sensor based on a phenomenological model for online estimation of the density and viscosity of a slurry flowing through a pipe-and-fittings assembly(PFA). The model is developed considering the conservation principle applied to mass and momentum transfer and considering frictional energy losses to include the variables directly affecting slurry properties. A reported proposal for state observers with unknown inputs is used to develop the first block of the observer structure. The second block is constructed with two options for evaluating slurry viscosity, generating two possible estimator structures, which are tested using real data. A comparison between them indicates different uses and capabilities according to available process information.

关键词： Soft sensor phenomenological based semi-physical model non-Newtonian fluids unknown input observer slurry flow

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Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist

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World Journal of Gastroenterology 2017年第5期23卷 899-905页

作者： Marie Sinclair Eduard Poltavskiy jennifer L Dodge jennifer c Lai Gastroenterology and Hepatology University of CaliforniaSan FranciscoCa 94143United States

AIMTo investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant *** listed for liver transplantation at a single centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios (IRR).RESULTSOf 587 cirrhotics, 64% were male, median age (interquartile range) was 60 (53-64) years and MELD score was 15 (12-18). Median Fried Frailty Index was 2 (1-3); 31.6% were classified as frail (fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1 hospitalisation; 38% of which involved major infection. 107/184 (58%) frail and 142/399 (36%) non-frail patients were hospitalised at least once (P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year (IRR = 1.51, 95%cI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender (IRR for frailty of 1.21, 95%cI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by *** cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity.

关键词： Hospitalisation Infection cirrhosis Frailty Transplantation

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Tertiary lymphoid structures in cancer – considerations for patient prognosis

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cellular & Molecular Immunology 2020年第6期17卷 570-575页

作者： Luis munoz-Erazo Janet L.Rhodes Valentine c.Marion Roslyn A.Kemp Department of Microbiology and Immunology University of OtagoDunedinNew Zealand Ecole Normale Superieure de Lyon LyonFrance and Universite Claude Bernard Lyon 1LyonFrance

Tertiary lymphoid structures(TLS)are ectopic lymphoid formations that form within nonlymphoid *** share structural and functional characteristics with secondary lymphoid structures such as lymph nodes and can contain B-cell follicles and germinal centers surrounded by a T-cell *** have been described in several types of cancers and are usually associated with positive patient ***,TLS differ vastly in cellular composition and location within tissue *** this review,we discuss factors confounding the interpretation of the evidence for a prognostic role for TLS in cancer and frame these factors in the context of translation to regular clinical use.

关键词： tertiary lymphoid structure prognosis cancer tissue

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The Roles of Different cLE Domains in Arabidopsis cLE Polypeptide Activity and Functional Specificity

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Molecular Plant 2010年第4期3卷 760-772页

作者： Ling Meng Kenneth c. Ruth jennifer c. Fletcher Lewis Feldman Department of Plant and Microbial Biology 111 Koshland Hall University of California Berkeley CA 94720-3102 USA Plant Gene Expression center USDA-UC Berkeley 800 Buchanan Street Albany CA 94710 USA

The cLE （cLVATA3/ESR-related） family of plant polypeptide signaling molecules shares a conserved 14-aminoacid （aa） motif, designated the cLE motif, which recent studies suggest is sufficient for cLE function in vitro. In this study, we report that Arabidopsis cLE proteins can function in a tissue-specific manner and confirm some cLE factors can act through different receptors. Using domain swapping, we show for the first time that the cLE motif likely determines much of the functional tissue-specificity of the proteins in planta. However, we also provide evidence in support of the new view that sequences outside the cLE motif （14 aa） contribute to cLE function and functional specificity in vivo. Additionally, we report that deletion of the putative signal peptide from different cLE proteins completely inactivates cLE function in vivo, whereas exchanging the cLE signal peptides with a conventional signal peptide from a rice glycine-rich cell wall protein also influences cLE function. We thus propose that the cLE motif itself determines its functional tissue-specificity by dic- tating the direct recognition and interaction of each cLE peptide with its optimal receptor（s）, whereas the receptor（s） may be available in a tissue-specific manner. On the other hand, the sequences outside the cLE motif may influence cLE function by affecting the processing of cLE peptides, resulting in a change in the availability and/or abundance of cLE peptides in specific tissues and/or cells.

关键词： Arabidopsis cell signaling cLE meristem polypeptide protein domain.

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Perinatal transmission in infants of mothers with chronic hepatitis B in california

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World Journal of Gastroenterology 2017年第27期23卷 4942-4949页

作者： jennifer c Burgis Darryl Kong catheryn Salibay jennifer Zipprich Kathleen Harriman Samuel So Department of Pediatrics Stanford University california Department of Public Health Immunization Branch Asian Liver center Stanford University

To evaluate maternal hepatitis B virus (HBV) DNA as risk for perinatal HBV infection among infants of HBV-infected women in california. METHODSRetrospective analysis among infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received post vaccination serologic testing (PVST) between 2005 and 2011 in california. Demographic information was collected from the california Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen (HBeAg) status were obtained from three large commercial laboratories in california and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/mL, a 5:1 ratio of cases to controls and a two-sided confidence level of 95%. RESULTSA total of 17687 infants were born to HBsAg positive mothers in california between Jan 1 2005 and Dec 31, 2011. Among 11473 infants with PVST, only 125 (1.1%) were found to be HBV infected. Among these infected infants, lapses in Advisory committee on Immunization Practices recommended post exposure prophylaxis (PEP) occurred in only 9 infants. However, PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBeAg and HBV DNA level, case-control analysis found HBeAg positivity (70.4% vs 28.9%, OR = 46.76, 95%cI: 6.05-361.32, P 7 IU/mL (92.6% vs 18.5%, OR = 54.5, 95%cI: 12.22-247.55, P ciated with perinatal HBV infection. In multivariate logistic regression, maternal HBV DNA level ≥ 2 × 107 IU/mL was the only significant independent predictor of perinatal HBV infection. cONcLUSIONIn california, tra

关键词： Perinatal transmission Hepatitis B virus DNA Pregnancy Hepatitis B Vaccination Post-vaccine serology testing

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Effects of music and video on perceived exertion during high-intensity exercise

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Journal of Sport and Health Science 2017年第1期6卷 81-88页

作者： Enoch c.chow jennifer L.Etnier Department of Kinesiology University of North Carolina at GreensboroGreensboroNC 27412USA

Background: Dissociative attentional stimuli(e.g., music, video) are effective in decreasing ratings of perceived exertion(RPE) during low-tomoderate intensity exercise, but have inconsistent results during exercise at higher intensity. The purpose of this study was to assess attentional focus and RPE during high-intensity exercise as a function of being exposed to music, video, both(music and video), or a no-treatment control ***: During the first session, healthy men(n = 15) completed a maximal fitness test to determine the workload necessary for high-intensity exercise(operationalized as 125% ventilatory threshold) to be performed during subsequent sessions. On 4 subsequent days, they completed 20 min of high-intensity exercise in a no-treatment control condition or while listening to music, watching a video, or both. Attentional focus, RPE,heart rate, and distance covered were measured every 4 min during the ***: Music and video in combination resulted in significantly lower RPE across time(partial η~2= 0.36) and the size of the effect increased over time(partial η~2= 0.14). Additionally, music and video in combination resulted in a significantly more dissociative focus than the other conditions(partial η~2= 0.29).conclusion: Music and video in combination may result in lower perceived exertion during high-intensity exercise when compared to music or video in isolation. Future research will be necessary to test if reductions in perceived exertion in response to dissociative attentional stimuli have implications for exercise adherence.

关键词： Acute exercise Attentional focus Effort Perceived exertion

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Response to strict and liberalized specific carbohydrate dietin pediatric crohn's disease

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World Journal of Gastroenterology 2016年第6期22卷 2111-2117页

作者： jennifer c Burgis Kaylie Nguyen KT Park Kenneth cox Department of Pediatrics GastroenterologyHepatology and NutritionStanford University School of MedicinePalo AltoCA 94304United States

AIM: To investigate the specific carbohydrate diet(ScD) as nutritional therapy for maintenance of remission in pediatric crohn's disease(cD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with cD who initiated the ScD as therapy at time of diagnosis or flare. Two groups defined as ScD simple(diet alone, antibiotics or 5-ASA) or ScD with immunomodulators(corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and ***: The mean age at start of the ScD was 11.8 ± 3.0 years(range 6.6-17.6 years) with five patients starting the ScD within 5 wk of diagnosis. Three patients maintained a strict ScD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo(range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict ScD and appeared stable after liberalization(P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict ScD, with small loss in weight percentile documented with liberalization. cONcLUSION: Disease control may be attainable with the ScD in pediatric cD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

关键词： Specific carbohydrate diet crohn's disease Pediatrics Nutrition therapy

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Optical tissue clearing enables rapid,precise and comprehensive assessment of three-dimensional morphology in experimental nerve regeneration research

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Neural Regeneration Research 2022年第6期17卷 1348-1356页

作者： Simeon c.Daeschler jennifer Zhang Tessa Gordon Gregory H.Borschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Indiana University School of Medicine IndianapolisINUSA

Morphological analyses are key outcome assessments for nerve regeneration studies but are historically limited to tissue *** optical tissue clearing techniques enabling three-dimensional imaging of entire organs at a subcellular resolution have revolutionized morphological studies of the *** extend their applicability to experimental nerve repair studies we adapted these techniques to nerves and their motor and sensory targets in *** solvent-based protocols rendered harvested peripheral nerves and their target organs transparent within 24 hours while preserving tissue architecture and *** optical clearing was compatible with conventional laboratory techniques,including retrograde labeling studies,and computational image segmentation,providing fast and precise cell ***,optically cleared organs enabled three-dimensional morphometry at an unprecedented scale including dermatome-wide innervation studies,tracing of intramuscular nerve branches or mapping of neurovascular *** their wide-ranging applicability,rapid processing times,and low costs,tissue clearing techniques are likely to be a key technology for next-generation nerve repair *** procedures were approved by the Hospital for Sick children’s Laboratory Animal Services committee(49871/9)on November 9,2019.

关键词： histology image segmentation morphometry nerve regeneration outcome assessment peripheral nerve three-dimensional imaging tissue clearing

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